Tension prolongation during recovery from myocardial hypoxia

We tested the hypothesis that the intracellular Ca2" overload of ventricular myocardium during the period of posthypoxic reoxygenation is mediated by transsarcolemmal Ca2" influx via Na + /Ca2+ exchange. In aequorin-loaded, ferret right ventricular papillary muscles, blockers of the sarcolemmal and the sarcoplasmic reticulum Ca2" channels, slowed the Ca?' transient, producing a convex ascent during membrane depolarization, followed by a concave descent during repolarization. The magnitude of the Ca, transient was affected by changes in the membrane potential, Nat, Na4, and Ca2+, and was blocked by Ni2+, or dichlorbenzamil. The calculated Na+/Ca2' exchange current was in the reverse mode (Ca2+ influx) during the ascending phase of the Ca2+ transient, and was abruptly switched to the forward mode (Ca2+ efflux) at repolarization, matching the time course of the CaF+ transient. During hypoxic superfusion, the Ca transient was abbreviated, which was associated with a shorter action potential duration. In contrast, immediately after reoxygenation, the Ca?' transient increased to a level greater than that of the control, even though the action potential remained abbreviated. This is the first demonstration on a beat-to-beat basis that, during reoxygenation, Ca2+ influx via Na+/Ca2+ exchange is augmented and transports a significant amount of Ca2+ into the ventricular myocardial cell. The activation of the exchanger at the time of reoxygenation appears to be mediated by Na+ accumulation, which occurs during hypoxia. (J. Clin. Invest. 1994.93:1275-1284

Section: Resultsmentioning

confidence: 58%

“…Of interest, while the durations of Ca?' transients were abbreviated by the transition from hypoxia to reoxygenation, tension relaxation was prolonged after reoxygenation ( 19,32,62). This discrepancy between Ca?'…”

Section: Resultsmentioning

confidence: 99%

Sodium/calcium exchange modulates intracellular calcium overload during posthypoxic reoxygenation in mammalian working myocardium. Evidence from aequorin-loaded ferret ventricular muscles.

Kihara¹,

Sasayama²,

Inoko³

et al. 1994

“…In contrast to the observations with low coronary flow global ischemia, hypoxia (anaerobic perfusate at control coronary flow) in this experimental model consistently caused a rise in LVEDP. This was associated with a substantial prolongation of the time constant of left ventricular relaxation, T. It is important to point out that the rise in LVEDP relative to volume, as well as the substantial prolongation of T (+300 to +500% increase) occurred during hypoxia, and within 2 min of its onset; this is distinct from the phenomenon of tension prolongation during reoxygenation following hypoxia or ischemia, as described by others (32)(33)(34). When pacing tachycardia was superimposed on hypoxia, increases in T of 500% occurred in the posttachyeardia period prior to reoxygenation, and were associated with more than a doubling of LVEDP.…”

Section: Resultsmentioning

confidence: 67%

Comparison of Acute Alterations in Left Ventricular Relaxation and Diastolic Chamber Stiffness Induced by Hypoxia and Ischemia

Serizawa¹,

Vogel²,

Apstein³

et al. 1981

134

A B S T R A C T To clarify conflicting reports concerning the effects of ischemia on left ventricular chamber stiffness, we compared the effects of hypoxia at constant coronary perfusion with those of global ischemia on left ventricular diastolic chamber stiffness using isolated, perfused rabbit hearts in which the left ventricle was contracting isovolumically. Since chamber volume was held constant, increases in left ventricular end diastolic pressure (LVEDP) reflected increases in chamber stiffness. At a control coronary flow rate (30 ml/min), 2 min of hypoxia and pacing tachycardia (4.0 Hz) produced major increases in postpacing LVEDP (10±+1 to 24+3 mm Hg, P < 0.01) and the relaxation time constant, T, (40+4 to 224±37 ms, P < 0.001), while percent lactate extraction ratio became negative (+18±2 to -48±15%, P < 0.001). Coronary perfusion pressure decreased (72+5 to 52±3 mm Hg, P < 0.01), and since coronary flow was held constant, the fall in coronary perfusion pressure reflected coronary dilation and a decrease in coronary vascular resistance. Following an average of 71±6 s reoxygenation and initial heart rate (2.0 Hz), LVEDP and relaxation time constant T returned to control. Hypoxia alone (without pacing tachycardia) produced similar although less marked changes (LVEDP, 10-+-1 to 20+3 mm Hg; and T, 32±3 to 119+22 ms; P < 0.01 for both) and there was a strong correlation between LVEDP and T (r = 0.82, P < 0.001).When a similar degree of coronary vasodilatation was induced with adenosine, no change in LVEDP Received for publication 7 July 1980 and in revised form 6 October 1980. occurred, indicating that the increase in end diastolic pressure observed during hypoxia was not secondary to vascular engorgement, but due to an acute effect of hypoxia on the diastolic behavior of the ventricular myocardium.In contrast, global ischemia produced by low coronary flow (12-15 ml/min) resulted in a decrease in LVEDP, as well as a marked fall in left ventricular systolic pressure. In 14 global ischemia experiments, pacing tachycardia led to a further decline in left ventricular systolic pressure, and no increase was noted in postpacing LVEDP. Changes in lactate extraction ratio were much smaller in magnitude than with hypoxia and constant coronary perfusion. In two experiments (one at normal coronary flow and one at 15 ml/min), left ventricular systolic pressure did not change markedly from control when tachycardia was superimposed, and postpacing LVEDP showed a marked rise (to >25 mm Hg), which gradually recovered over 1-2 min at the control heart rate.From these results, we conclude that left ventricular chamber stiffness increases when myocardial 02 demand exceeds supply. This change is usually masked in ischemic (reduced coronary flow) preparations, perhaps because of reduced turgor of the coronary vascular bed, marked reductions in systolic work (and therefore myocardial 02 requirements), and local accumulation of hydrogen ion and metabolites following acute severe reduction of coronary flow. The increased chamber...

“…Previous studies using the isometrically contracting papillary muscle preparation have reported a shortened time of relaxation associated with hypoxia (8)(9)(10). This finding is most probably a function of two factors.…”

mentioning

confidence: 83%

“…To date, however, hypoxia, a major component of the ischemic state, has not been shown to impair the relaxation of cardiac muscle (8)(9)(10).…”

mentioning

confidence: 99%

Effect of Hypoxia on Myocardial Relaxation in Isometric Cat Papillary Muscle

Frist¹,

Palacios²,

Powell³

1978

A B S T R A C T Myocardial relaxation is an important energy-dependent process. Hypoxia, unlike ischemia, has not been shown to impair myocardial relaxation. This difference may be because (a) the traditional index to assess isometric muscle relaxation (halftime to relaxation or RT,/2) reflects both changes in developed tension as well as relaxation and (b) the relaxation process is highly sensitive to temperature and previous papillary muscle studies have been conducted under hypothermic conditions. The present study examines the effect of hypoxia on the relaxation process of 31 isometrically contracting kitten papillary muscles at hypothermic (29°C) and euthermic (38°C) conditions using RT112, the peak rate of tension fall (-dT/dt) and -dT/dt normalized for tension ([peak -dT/dt]/T and max [-dT/dt per T]). Hypoxia at 29°C resulted in a fall in RT,/2 from 278±11 (SEM) to 230±17 ms (P < 0.01) and no change in (peak -dTIdt)/T and max (-dTldt per T). However, at 38°C, hypoxia impaired relaxation as reflected in a prolongation of RTI/2 from 101±6 to 126±8 ms (P < 0.01) in spite of a substantial fall in peak tension. Moreover, (peak -dTIdt)IT decreased from -15.4±0.7 to -11.0±0.8/s (P <0.01) and max (-dT/dt per T) decreased from -25.1±1.8 to -13.8±0.9/s (P < 0.01). In conclusion, the present study demonstrates that hypoxia impairs the relaxation process of cardiac muscle.